Lactoferrin (LF) is an iron-binding protein synthesized by neutrophils and glandular epithelial cells. LF has been detected in most of the major secretions that bathe human mucosal surfaces; including saliva. Previous studies have indicated that LF can reversibly inhibit the growth of a variety of microorganisms by binding available iron making it inaccessible to the bacteria. This inhibition is readily reversed by the addition of exogenous iron. Recent studies in our laboratory have indicated that LF is capable of a direct irreversible inhibition of certain bacteria. This bactericidal effect is dependent on the chelating properties of LF. A survey of microorganisms indicated that a number of oral microorganisms was susceptible to the bactericidal activity of LF, suggesting a potentially potent mechanism of the regulation of the oral flora by salivary LF. Bacterial resistance to LF appears to be associated with the virulence of the organism. Current studies are being directed at the kinetics of action of LF and assessing the effects of LF on various bacterial components. Through such studies it might be possible to determine the mechanism of bacterial resistance and indirectly the mode of LF action. Possible interactions between LF and other salivary components such as antibody, lysozyme, and lactoperoxidase are also being investigated with either purified components or in saliva from various immune deficient and control subjects. The in situ effects of LF in dental plaque and plaque free-fluid by quantitation and analysis of localization of LF. The effects of LF on colonization, metabolism and macromolecular synthesis of various oral microorganisms are being evaluated in in vitro systems.